With the introduction of effective antidepressants, pharmacotherapy has not been limited exclusively to the psychiatrically ill, but has been expanded to include medically ill patients exhibiting depressive symptomatology as well. This has led to problems in diagnostic differentiation and, just as important, problems with interactions resulting from multiple medications. By describing the coexistence of depressive symptomatology in a large variety of physical illness, the physician is alerted to the complexities of psychiatric illness in the medically ill patient as well as the caution necessitated by the poly-pharmacotherapy required in this population.